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COMP: a candidate molecule in the pathogenesis of systemic sclerosis with a potential as a disease marker
  1. R Hesselstrand1,
  2. A Kassner2,
  3. D Heinegård2,
  4. T Saxne1
  1. 1
    Department of Clinical Sciences, Section for Rheumatology, Lund University, Sweden
  2. 2
    Department of Experimental Medical Sciences, Section for Connective Tissue Biology, Lund University, Sweden
  1. R Hesselstrand, Department of Rheumatology, Lund University Hospital, S-221 85 Lund, Sweden; roger.hesselstrand{at}skane.se

Abstract

Objective: Cartilage oligomeric matrix protein (COMP), primarily found in cartilage, is thought to be an important regulator of assembly and maintenance of the fibrillar collagen I and II networks. Recently, COMP was shown to be produced by skin fibroblasts from patients with systemic sclerosis (SSc, or scleroderma). The purpose of this study was to examine whether COMP is released from skin to serum in patients with SSc, and may serve as indicator of activity of skin involvement.

Methods: Serum COMP levels were measured by enzyme linked immunosorbent assay in patients with SSc whose skin involvement was assessed with the modified Rodnan skin score (mRss) and high frequency ultrasound. The presence of COMP in skin biopsies was assessed by Western blot using a monoclonal antibody specific for the very C-terminal end of human COMP.

Results: Serum COMP correlated to skin involvement as measured by the mRss (n = 70; rS = 0.60; p<0.001), to skin thickness measured by ultrasound (n = 88; rS = 0.55; p<0.001) and inversely to skin echogenicity measured by ultrasound (n = 88; rS = −0.40; p<0.001). In 70 patients followed longitudinally there was a correlation between changes in serum COMP (n = 307) and changes in mRss (rS = 0.35; p = 0.008). In individual patients monitored with repeated measurements, serum COMP changes closely paralleled changes in mRss. A C-terminal COMP fragment, with an apparent molecular mass of 56 kDa, was identified in SSc skin biopsies, while no COMP reactivity was detected in normal skin.

Conclusion: The high turnover of COMP in SSc skin suggests a pathophysiological role. Serum COMP shows promise as a new biomarker in SSc.

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Footnotes

  • RH and AK contributed equally to the study.

  • Funding: This study was supported by grants from the Swedish Medical Research Council, the Medical Faculty of Lund University, the Swedish Rheumatism Association, King Gustaf V 80-year Fund, the Österlund Foundation, the Kock Foundation and the European Community’s FP6 funding (AUTOCURE project) and the Anna-Greta Crafoord stiftelse (AK).

  • Competing interests: DH and TS are cofounders and minor shareholders of AnaMar Medical, Lund, Sweden. This publication only reflects the author’s views. The European Community is not liable for any use that may be made of the information herein.

  • Ethics approval: The study was approved by the regional ethics board.

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